Synthesis and characterization of N-tolyglycosylamines

Article abstract of DOI:10.1007/s10600-008-9095-y

N-Tolylglycosylamines were synthesized from o-, m-, and p-toluidines and aldoses (D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, and L-arabinose). The anomeric and isomeric compositions of the synthesized products were established using ^13<

Full text of DOI:10.1007/s10600-008-9095-y

Chemistry of Natural Compounds, Vol. 44, No. 4, 2008
SYNTHESIS AND CHARACTERIZATION OF N-TOLYLGLYCOSYLAMINES
R. I. Kublashvili, M. O. Labartkava,
K. P. Giorgadze, and D. Sh. Ugrekhelidze*
UDC 547.917
N
o m
p
-Tolylglycosylamines were synthesized from -, -, and -toluidines and aldoses (D-glucose, D-galactose,
D-mannose, L-rhamnose, D-xylose, and L-arabinose). The anomeric and isomeric compositions of the
13
synthesized products were established using C NMR methods.
Keywords: N-tolylglycosylamines, aldoses, D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, L-arabinose.
Toluidines characteristically have high physiological activity [1, 2]. One of the possible cellular metabolic pathways
of toluidines is their -glycosylation, as a result ofwhich the activityis considerablychanged [3]. The -glycosylation products
N
N
of toluidines have been investigated. Their anomers were identified using PMR and gamma-resonance spectroscopy [4, 5].
13
C NMR spectroscopy made it possible to study the rotational isomerism around the -glycoside bonds. The principal
N
13
parameter of C NMR spectroscopy is the chemical shift, which provides important information about the conformation [6].
Our goal was to investigate the -glycosylation of -, -, and -toluidines by aldoses (D-glucose, D-galactose, D-mannose,
o m
N
p
L-rhamnose, D-xylose, and L-arabinose) and tostudythe anomeric and isomeric compositions ofthe synthesized products using
13
C NMR methods.
Ofall methods for preparing -glycosides with aromatic aglycons (direct reaction ofsugars and amines, synthesis from
N
derivatives of sugars and amines,
-glycosylation), direct synthesis by reaction of unsubstituted monosaccharides and
trans
aromatic amines of moderate basicity (pK 1-6) is a convenient method for preparing these compounds [7-9]. The pK values
a
a
for -, -, and -toluidines are 4.39, 4.60, and 5.12, respectively. It is known that the yield of the target -glycoside is strongly
o m
p
N
influenced by the basicity of the starting amine. The higher the basicity of the amine is, the easier the resulting -glycoside
N
undergoesvarioustransformations(hydrolysis, Amadori—Heyns rearrangement, melanoidineformation, etc.)[10]. Asaresult,
the preparative yield of the target -glycoside decreases as the basicityofthe starting amine increases. We selected the optimum
N
conditions for the -glycosylation considering the properties of the amine involved. This made it possible to isolate
N
quantitatively the target products from the reaction mixtures. After the appropriate workup (recrystallization, paper
chromatography and thin-layer chromatography over silica gel) and identification (melting point, IR spectrum, elemental
13
analysis), the synthesized -glycosides were investigated using C NMR spectra.
N
IR spectra of the -tolylglycosylamines (KBr, ν, cm −1): 3380-3325 (OH stretch), 2910-2860 (CH stretch), 1660-1600
N
(C H ), 1530-1520 ( -glycoside), 1550-1540 (CH deformation, C–OH stretch), 1375-1370 (CN stretch), 1290-1250 (OH
N
6
6
deformation, CO stretch), 1180-1170 (CN stretch, anomeric C1), 1060-1000 (carbohydrate ring), 850-800 and 780-750
( -glycosylamine pyranose ring), 650-640 (CN stretch of anomeric C1).
N
13
Tables 1 and 2 give the C NMR spectra of the -tolylglycosylamines. Carbon atoms of the carbohydrate part that
N
are bonded to primary and secondary alcohols of the aldoses resonate at the strongest field. Carbon atoms of the carbohydrate
part that are bonded to two electronegative atoms (O–C–N) resonate at the weakest field. It is known that the chemical shifts
of β-conformers of most monosaccharides (except mannose, rhamnose, and arabinose) are greater than those of the
α-conformers [6, 11, 12]. Therefore, resonances located at comparativelyweak field belong to the β-anomers; at comparatively
strong field, to the α-anomers. Resonances of C atoms of the aromatic part are situated in the range 110-149 ppm. The ratios
of β- to α-anomers were calculated taking into account the relaxation time of the anomeric C and the signal strength. These
data were used to calculate the isomeric and anomeric compositions of equilibrium mixtures of N-glycosides of isomorphous
aldose pairs (Table 2).
I. Javakhishvili Tbilisi State University, 0128, Georgia, Tbilisi, pr. I. Chavchavadze, 3, e-mail:
devi_ugrekhelidze@hotmail.com. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 333-335, July-August, 2008.
Original article submitted September 19, 2007.
0009-3130/08/4404-0413 ©2008 Springer Science+Business Media, Inc.
413

13
TABLE 1. Isomeric and Anomeric Compositions of N-Tolylglycosylamines and Chemical Shifts of C Atoms of the
Carbohydrate Fragments
13C chemical shift, ppm
N
Tolyl- -glycoside
Yield, %
mp, °C
/ , %
β α
C1
C2
C3
C4
C5
C6
N o
β
β
β
β
β
β
β
β
β
β
α
β
β
β
α
β
- -Tolyl- -D-glucopyranosylamine
78.0
89.0
81.0
70.6
81.7
83-84
100
100
100
100
100
84.3
15.7
100
100
75.8
24.2
100
100
73.3
26.7
100
100
100
65.1
34.9
71.4
28.6
85.4
85.3
85.5
85.9
82.5
86.0
88.2
80.9
81.4
81.7
84.1
80.6
81.1
81.3
83.8
86.0
86.0
86.4
85.5
88.5
85.7
88.7
73.0
73.1
73.2
68.4
72.2
70.4
82.5
71.2
71.2
71.3
70.8
72.4
72.5
72.4
72.4
74.9
73.4
73.2
70.8
70.3
70.8
69.7
73.1
77.3
77.1
73.9
73.5
74.3
76.1
74.4
74.5
74.6
71.1
71.3
72.1
72.1
72.9
76.9
77.8
77.9
70.6
73.5
70.6
73.5
70.5
70.3
70.4
70.3
70.2
69.5
83.2
67.1
67.1
67.2
67.9
74.1
74.2
74.2
70.9
70.2
70.1
70.4
70.4
69.7
70.4
69.5
77.3 61.2
77.7 61.1
77.7 61.1
75.5 60.6
76.1 62.9
75.5 60.6
70.8 62.8
77.8 61.2
77.8 61.3
77.8 61.3
72.6 61.3
67.7 17.2
71.3 18.1
71.3 18.0
70.8 18.0
N m
- -Tolyl- -D-glucopyranosylamine
123-124
101-102
122-123
107-108
N p
- -Tolyl- -D-glucopyranosylamine
N o
- -Tolyl- -D-galactopyranosylamine
N m
- -Tolyl- -D-galactopyranosylamine
N p
- -Tolyl- -D-galactopyranosylamine*
N p
- -Tolyl- -D-galactofuranosylamine*
66.8
92.8
93.0
134-135
143
155-156
N o
- -Tolyl- -D-mannopyranosylamine
N m
- -Tolyl- -D-mannopyranosylamine
N p
- -Tolyl- -D-mannopyranosylamine**
N p
- -Tolyl- -D-mannopyranosylamine**
85.4
79.0
87.0
158-159
128-129
126-127
N o
- -Tolyl- -L-rhamnopyranosylamine
N m
- -Tolyl- -L-rhamnopyranosylamine
N p
- -Tolyl- -L-rhamnopyranosylamine**
N o
- -Tolyl- -L-rhamnopyranosylamine**
79.0
72.0
75.0
70.0
112-113
103-104
115-117
122-123
N o
- -Tolyl- -D-xylopyranosylamine
65.8
66.5
66.5
63.5
67.8
63.5
67.8
-
-
-
-
-
-
-
N m
β
β
β
α
β
α
- -Tolyl- -D-xylopyranosylamine
N p
- -Tolyl- -D-xylopyranosylamine
N m
- -Tolyl- -L-arabinopyranosylamine**
N m
- -Tolyl- -L-arabinopyranosylamine**
74.0
68.0
94-95
97-98
N p
- -Tolyl- -L-arabinopyranosylamine**
N p
- -Tolyl- -L-arabinopyranosylamine**
______
Yield and mp for the forms of sugars (*): for isomeres (**).
TABLE 2. 13C Chemical Shifts of Atoms in Aromatic Fragments of N-Tolylglycosylamines and Their Anomeric
Compositions, %
13C chemical shift, ppm
N
Tolyl- -glycoside
%
C1
C2
C3
C4
C5
C6
CH3
N o
- -Tolyl- -D-glucopyranosylamine
β
146.2
147.3
145.0
144.8
149.0
144.5
144.8
143.6
146.2
143.9
144.8
143.6
146.2
143.8
144.6
144.8
123.5
114.0
113.3
122.1
113.3
113.3
113.7
122.0
114.3
113.8
113.5
121.7
114.2
113.7
113.2
122.5
131.1
137.7
129.2
129.7
137.6
129.2
129.3
129.9
137.7
129.3
129.2
129.9
137.8
129.2
129.2
130.0
118.8
118.0
125.4
117.2
116.6
125.3
125.6
117.4
118.2
125.7
125.4
117.4
118.2
125.7
125.3
117.7
128.1
128.7
129.2
126.6
128.6
129.2
129.3
126.8
128.6
129.3
129.2
126.7
128.7
129.2
129.2
126.8
113.0
110.5
113.3
111.5
110.1
113.3
113.7
111.8
110.9
113.8
113.5
111.7
110.9
113.7
113.2
111.7
17.4
21.4
20.2
17.4
21.4
20.2
20.2
17.2
21.4
20.2
20.2
18.1
21.4
20.1
20.1
17.7
100
100
100
100
100
84.3
15.7
100
100
75.8
24.2
100
100
73.3
26.7
100
N m
β
β
- -Tolyl- -D-glucopyranosylamine
N p
- -Tolyl- -D-glucopyranosylamine
N o
β
β
- -Tolyl- -D-galactopyranosylamine
N m
- -Tolyl- -D-galactopyranosylamine
N p
β
β
- -Tolyl- -D-galactopyranosylamine
N p
- -Tolyl- -D-galactofuranosylamine
N o
β
β
- -Tolyl- -D-mannopyranosylamine
N m
- -Tolyl- -D-mannopyranosylamine
N p
β
α
- -Tolyl- -D-mannopyranosylamine
N p
- -Tolyl- -D-mannopyranosylamine
N o
β
β
- -Tolyl- -L-rhamnopyranosylamine
N m
- -Tolyl- -L-rhamnopyranosylamine
N p
β
α
- -Tolyl- -L-rhamnopyranosylamine
N o
- -Tolyl- -L-rhamnopyranosylamine
N o
- -Tolyl- -D-xylopyranosylamine
β
414

TABLE 2. (continued)
13C chemical shift, ppm
Tolyl-N-glycoside
%
C1
C2
C3
C4
C5
C6
CH3
N-m-Tolyl-β-D-xylopyranosylamine
N-p-Tolyl-β-D-xylopyranosylamine
N-m-Tolyl-β-L-arabinopyranosylamine
N-m-Tolyl-α-L-arabinopyranosylamine
N-p-Tolyl-β-L-arabinopyranosylamine
N-p-Tolyl-α-L-arabinopyranosylamine
147.0
144.9
147.2
146.7
144.8
144.4
114.0
113.5
114.3
113.8
113.9
113.5
137.9
129.4
137.8
137.9
129.4
129.4
118.2
125.7
118.3
118.5
125.6
125.9
131.9
129.4
128.8
128.8
129.4
129.4
110.7
113.5
110.8
111.2
113.9
113.5
21.4
20.4
21.6
21.6
20.3
20.3
100
100
65.1
34.9
71.4
28.6
The furanose ring is unstable due to -interactions between neighboring substituents. The cyclic furanose forms of
cis
mannose, rhamnose, glucose, and xylose are especially unstable because of these interactions. For example, the number of
1,2- -interactions for mannose and rhamnose is two, where the interaction involves O /O and O /C . The number of 1,2-
-
cis
cis
-interactions are possible for the furanose forms of
2
3
3
5
interactions for glucose and xylose is one involving O /C . Only
trans
3
5
galactose and arabinose [13]. According to Table 1, the yields of the synthesized -tolylglycosylamines decreased in the order
N
mannose, rhamnose, glucose, xylose, galactose, and arabinose. Thus, the stable furanose forms of aldoses produce -glycosides
N
that are largely converted to melanoidines under the -glycosylation reaction conditions.
N
EXPERIMENTAL
13
IR spectra in KBr were recorded on a Specord 75 IR spectrophotometer; C NMR spectra, on a Bruker NM-250 MGH
instrument using (CD ) SO with a shift of the central resonance of 39.505 ppm with full C–H decoupling, weighed samples
3 2
(30 mg), and 60°C.
Synthesis of N-tolylglycosylamines [11, 12]. A mixture of aldose (0.01 mol) and toluidine (0.012 mol) in water
(0.5 mL) was heated to boiling on a water bath with stirring until complete dissolution of the starting materials. The reaction
mixture was cooled to room temperature, treated with diethylether (40 mL), stirred, and left overnight at room temperature.
The resulting crystalline precipitate was filtered off, ground with ethanol (96%), treated with diethylether, and thoroughly
mixed. The precipitate was filtered off. The resulting -glycoside was purified by reprecipitation from alcoholic diethylether.
N
The purity of the products was monitored by TLC on Silufol UV-254 plates (for toluidines, benzene:ethanol, 9:1; for aldoses,
CHCl :CH OH, 19:5; for -tolylglycosylamines, dioxane:benzene, 1:4). Sugarsweredevelopedbya basic solution ofpotassium
N
3
3
permanganate and sodium metaperiodate; toluidines, by alcoholic -dimethylaminobenzaldehyde.
p
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